Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer
Abstract Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant‐specific morphological criteria and high signal‐to‐noise in mutation‐based diagnosis, resp...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202404491 |
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| author | Guangzhe Zheng Shaobo Chen Wanqi Ma Quanshu Wang Li Sun Changwen Zhang Ge Chen Shuping Zhang Shuguang Chen |
| author_facet | Guangzhe Zheng Shaobo Chen Wanqi Ma Quanshu Wang Li Sun Changwen Zhang Ge Chen Shuping Zhang Shuguang Chen |
| author_sort | Guangzhe Zheng |
| collection | DOAJ |
| description | Abstract Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant‐specific morphological criteria and high signal‐to‐noise in mutation‐based diagnosis, respectively. Importantly, intratumor heterogeneity is largely lost in current molecular classification system, which can be resolved by single cell RNA sequencing (scRNA‐seq). However, scRNA‐seq loses spatial information and morphological features. Herein, scRNA‐seq is integrated and spatially‐resolved transcriptomics (SRT) to elaborate the mechanisms underlying the spatial heterogeneity, malignancy and metastasis of PTCs by associating transcriptome and local morphology. This results demonstrated that PTC cells evolved with multiple routes, driven by the enhanced aerobic metabolism and the suppressed mRNA translation and protein synthesis and the involvement of cell–cell interaction. Two curated malignant and metastatic footprints can discriminate PTC cells from normal thyrocytes. Ferroptosis resistance contributed to PTC evolution. This results will advance the knowledge of intratumor spatial heterogeneity and evolution of PTCs at spatial and single‐cell levels, and propose better diagnostic strategy. |
| format | Article |
| id | doaj-art-f717e4fe915146eba253ff6eb67d90b4 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-f717e4fe915146eba253ff6eb67d90b42025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202404491Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid CancerGuangzhe Zheng0Shaobo Chen1Wanqi Ma2Quanshu Wang3Li Sun4Changwen Zhang5Ge Chen6Shuping Zhang7Shuguang Chen8Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 ChinaDepartment of General Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100032 ChinaMedical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 ChinaMedical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 ChinaThe First Affiliated Hospital of Shandong First Medical University Jinan Shandong 250014 ChinaDepartment of Urology Tianjin Institute of Urology The Second Hospital of Tianjin Medical University Tianjin 300211 ChinaDepartment of General Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100032 ChinaMedical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong 250117 ChinaDepartment of General Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100032 ChinaAbstract Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant‐specific morphological criteria and high signal‐to‐noise in mutation‐based diagnosis, respectively. Importantly, intratumor heterogeneity is largely lost in current molecular classification system, which can be resolved by single cell RNA sequencing (scRNA‐seq). However, scRNA‐seq loses spatial information and morphological features. Herein, scRNA‐seq is integrated and spatially‐resolved transcriptomics (SRT) to elaborate the mechanisms underlying the spatial heterogeneity, malignancy and metastasis of PTCs by associating transcriptome and local morphology. This results demonstrated that PTC cells evolved with multiple routes, driven by the enhanced aerobic metabolism and the suppressed mRNA translation and protein synthesis and the involvement of cell–cell interaction. Two curated malignant and metastatic footprints can discriminate PTC cells from normal thyrocytes. Ferroptosis resistance contributed to PTC evolution. This results will advance the knowledge of intratumor spatial heterogeneity and evolution of PTCs at spatial and single‐cell levels, and propose better diagnostic strategy.https://doi.org/10.1002/advs.202404491intratumor spatial heterogeneitypapillary thyroid cancerspatial evolutionspatially‐resolved transcriptomics |
| spellingShingle | Guangzhe Zheng Shaobo Chen Wanqi Ma Quanshu Wang Li Sun Changwen Zhang Ge Chen Shuping Zhang Shuguang Chen Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer Advanced Science intratumor spatial heterogeneity papillary thyroid cancer spatial evolution spatially‐resolved transcriptomics |
| title | Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer |
| title_full | Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer |
| title_fullStr | Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer |
| title_full_unstemmed | Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer |
| title_short | Spatial and Single‐Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer |
| title_sort | spatial and single cell transcriptomics unraveled spatial evolution of papillary thyroid cancer |
| topic | intratumor spatial heterogeneity papillary thyroid cancer spatial evolution spatially‐resolved transcriptomics |
| url | https://doi.org/10.1002/advs.202404491 |
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